The current year is devoted to continuing the studies dealing with mitochondrial biogenesis in mammalian tissue culture cells. A primary goal will be the isolation and characterization of cell lines which are resistant to mitochondrial protein synthesis inhibitors other than chloramphenicol. These cell lines will be examined to determine if the antibiotic resistance resides in the cytoplasm. The availability of different cytoplasmically (mitochondrial) coded markers will make it possible to select for recombination events within the mitochondrial genome. The method of introducing the resistant mitochondrial into a recipient cell will be either by cell-cell hybridization or by fusing an enucleated resistance cell fragment with a sensitive cell.